Description
Date/Time: 04-03-2018 - Tuesday - 05:00 PM - 07:00 PM
In-Kyu Park1 Kondareddy Cherukula1 Chong-Su Cho2

1, Chonnam National University, Hwasun, , Korea (the Republic of)
2, Seoul National University, Seoul, , Korea (the Republic of)

Peritoneal carcinomatosis (PC) is a fatal condition arising in gastrointestinal tract characterized by poor prognosis and poor understanding of the disease. PC patients administered drugs locally in the tumor region such as intraperitoneal chemotherapy, often suffer from low drug retention time and tumor penetration. Herein, we synthesized Lithocholic acid (LCA)-conjugated disulfide-linked polyethyleneimine (ssPEI) micelle nanoconstruct by covalently conjugating ssPEI and LCA, thereby forming nano-micellar structures which loaded with paclitaxel (LAPMi-PTX) drug for IPCh. Incorporation of positive surface charge aided in prolonged peritoneal retention presumably by ascites fluid-induced protein corona formation and the subsequent size expansion caused resistance against crossing the lymphatic openings for the undesired clearance. Furthermore, preferential tumor penetration by LAPMi-PTX is attributable to the permeation enhancing properties of LCA, and subsequent tumor activatable drug release was induced by the presence of the disulfide linkages. By integrating these properties, LAPMi exhibited prolonged peritoneal residence time, enhanced tumor permeation and chemotherapeutic effect clearly evidenced by in vitro tumor spheroid and in vivo studies. Importantly, our strategy enabled significant PC inhibition and the overall survival rate of tumor-bearing mice. In conclusion, we provided a new paradigm of intractable PC treatment by enabling the prolonged residence time of nanoconstruct and thereby enhancing tumor penetration and anti-tumor therapy.

Acknowledgements
This work was financially supported by Basic Science Research Program (No. 2016R1A2B4011184 & 2016K2A9A1A06921661) and the Pioneer Research Center Program (2014M3C1A3053035) through the National Research Foundation of Korea (NRF) funded by the Korean government, MSIP.

Meeting Program
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5:00 PM–7:00 PM Apr 3, 2018

PCC North, 300 Level, Exhibit Hall C-E